Richards J S, Hedin L
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Annu Rev Physiol. 1988;50:441-63. doi: 10.1146/annurev.ph.50.030188.002301.
As stated earlier, the mammalian ovary maintains the continuous development of follicles, but only a few are selected to ovulate and form corpora lutea. These processes are regulated primarily by the gonadotropins and involve specific, sequential changes in the function of theca cells and granulosa cells. Data from recent studies (summarized in Figure 3) show that specific genes are turned on or off at different stages of follicular growth in response to estradiol and different amounts of gonadotropins and cAMP. For example, mRNA for RII51 in granulosa cells and theca cells increases in association with small increased in cAMP but is markedly reduced by the LH surge and high cAMP. The content of mRNA for other kinase subunits, RI and C alpha, show little or no change during similar hormonal changes. In theca cells, mRNA for 17 alpha-hydroxylase increased and decreased in a manner similar to that for RII51. In contrast, levels of mRNA for P450scc increased only gradually in follicles but were markedly increased by the LH surge and high concentrations of cAMP and then appeared to be constitutively expressed in rat corpora lutea in a cAMP-independent manner. PGS and t-PA appear to follow yet another pattern: rapid induction by the LH surge followed by a rapid decline in association with ovulation. One major task for reproductive endocrinologists and molecular biologists now is to determine how low and high concentrations of cAMP act to turn on and turn off the expression of these specific genes at specific times during follicular maturation. A working model of the molecular events occurring in theca and granulosa cells of PO follicles is shown in Figure 4. LH acts on theca cells via cAMP ro regulate both P450scc and P450(17) alpha mRNA levels, leading to increased biosynthesis of androstenedione. The mechanisms by which cAMP acts in theca cells remain to be determined but appear to involve an increase in the content of RII51, P450scc, and P450(17) alpha. In granulosa cells, androstenedione is converted to estradiol by the aromatase P450 enzyme system. Estradiol, in turn, binds to estradiol receptors present in these cells and may thereby regulate gene expression. However, despite the presence of estradiol and estradiol receptors, little or no effect of estradiol is observed unless FSH acts via the FSH receptor to increase intracellular concentrations of cAMP. In a manner not yet understood, cAMP appears to enhance the actions of estradiol.(ABSTRACT TRUNCATED AT 400 WORDS)
如前所述，哺乳动物的卵巢维持卵泡的持续发育，但只有少数卵泡被选择排卵并形成黄体。这些过程主要由促性腺激素调节，涉及卵泡膜细胞和颗粒细胞功能的特定、连续变化。最近的研究数据（总结于图3）表明，在卵泡生长的不同阶段，特定基因会根据雌二醇、不同量的促性腺激素和环磷酸腺苷（cAMP）的变化而开启或关闭。例如，颗粒细胞和卵泡膜细胞中RII51的信使核糖核酸（mRNA）随着cAMP的少量增加而增加，但在促黄体生成素（LH）峰和高浓度cAMP作用下显著减少。在类似的激素变化过程中，其他激酶亚基RI和Cα的mRNA含量几乎没有变化。在卵泡膜细胞中，17α-羟化酶的mRNA以与RII51相似的方式增加和减少。相比之下，细胞色素P450侧链裂解酶（P450scc）的mRNA水平在卵泡中仅逐渐增加，但在LH峰和高浓度cAMP作用下显著增加，然后在大鼠黄体中似乎以不依赖cAMP的方式持续表达。前列腺素合成酶（PGS）和组织型纤溶酶原激活剂（t-PA）似乎遵循另一种模式：在LH峰作用下迅速诱导，随后在排卵时迅速下降。生殖内分泌学家和分子生物学家目前的一项主要任务是确定低浓度和高浓度的cAMP如何在卵泡成熟的特定时间开启和关闭这些特定基因的表达。图4展示了初级卵泡（PO）的卵泡膜细胞和颗粒细胞中发生的分子事件的工作模型。LH通过cAMP作用于卵泡膜细胞，调节P450scc和P450（17）α的mRNA水平，导致雄烯二酮的生物合成增加。cAMP在卵泡膜细胞中的作用机制尚待确定，但似乎涉及RII51、P450scc和P450（17）α含量的增加。在颗粒细胞中，雄烯二酮通过芳香化酶P450酶系统转化为雌二醇。反过来，雌二醇与这些细胞中存在的雌二醇受体结合，从而可能调节基因表达。然而，尽管存在雌二醇和雌二醇受体，但除非促卵泡生成素（FSH）通过FSH受体作用增加细胞内cAMP浓度，否则几乎观察不到雌二醇的作用。以一种尚不清楚的方式，cAMP似乎增强了雌二醇的作用。（摘要截选至400字）
